The project is devoted to elucidating mechanisms responsible for the hypercoagulable state and developing methodology for studying mucopolysaccharide antithrombin interactions under a variety of conditions; specifically we intend: (a) to examine the interaction of hemostatic system enzymes with antithrombin and highly active heparin; (b) to determine the structural basis of heparin's anticoagulant action; (c) to probe the molecular details of the heparin-antithrombin-enzyme interaction; (d) to analyze heparin fractions with multiple binding sites for antithrombin; (e) to study the pharmacologic function of highly active heparin and the physiologic function of heparin-like molecules on the vessel wall.